ABSTRACT Deficits in cognitive-EF (executive function) are frequently seen early in PD and progress, resulting in disruption of daily activities. People with PD are often impaired in real life situations in which more than one activity needs to be performed at a time. This Merit Review Proposal compares efficacy of two rehabilitation interventions to reduce cognitive-EF deficits and improve both dual tasking (DT) abilities and instrumented activities of daily living (IADLs) in veterans and others with Parkinson's Disease (PD). Interventions are:(1) a treadmill exercise program with aerobic training (TAEX) (2) a computerized cognitive training program (TCOG). These two rehabilitation regimens will be compared alone and in combination. The study will provide insight into individual and synergistic effects of these interventions and optimal rehabilitation strategies to improve cognitive and functional performance in PD. We hypothesize that combined 3 months of TAEX+TCOG will be more effective to improve cognitive- EF domains, DT performance, and IADLs compared to either of these regimens alone. Because the natural history of EF decline has not been well characterized in PD with different levels of the disease, we will also employ a delayed entry control group that will further enable us to determine whether any of these treatment modalities is more effective than no intervention. We hypothesize that treatment effects of TAEX + TCOG will be retained for a period of 3 months following the intervention. The specific aims of this project are: (1) To compare the efficacy of TAEX versus TCOG versus TAEX + TCOG as interventions to improve EF in PD (2) To compare the efficacy of TAEX versus TCOG versus TAEX + TCOG as interventions to improve Dual Task (DT) performance in PD (3) To investigate whether improvement in DT performance translates into improved ability to conduct Instrumental Activities of Daily Living (IADLs). Each intervention will last 3 months. The TAEX intervention will consist of progressive treadmill exercise with aerobic training 3 times/week, with a conservative start of 20 mins. per session progressive to 45 mins. The TCOG intervention will consist of computerized cognitive training 3 times/week for 30 mins. The combined TAEX + TCOG intervention will last 1 hour and 30 mins. Subjects in the control group (delayed entrance) will go through a period of no intervention for 3 month baseline. During baseline they will not exercise or participate in any cognitive training activities. Following the baseline period they will be assigned to one of the intervention groups and will go through the exercise protocol of their respective group. Outcome measures will include: (1) Neuropsychological assessment with paper-and-pencil and computer- based tests of EF, (2) DT with a "walking while talking" paradigm, (3) daily activity measures (4) Psychiatric Measures (5) Cardiorespiratory Function Measures. Currently there is no effective treatment for the specific cognitive deficits caused by PD. No studies have investigated the potential benefits of rehabilitation strategies to improve such deficits. The proposed work will help generate new knowledge about rehabilitation models for cognitive impairment and cognitive-related disability in patients with PD. They will pave the way for multi-center clinical trials, producing efficacy data on which clinical practice can be based. PUBLIC HEALTH RELEVANCE: Project Narrative: Parkinson's Disease (PD) affects men with a higher frequency than women. Onset of PD is generally between the fifth and seventh decades;3 percent of people over 65 have PD. Given that the VA population is predominantly male and aging, significant numbers of veterans will develop PD in the coming years. Testing practical interventions that could slow decline in cognitive abilities and consequent impairments of daily function carries a broad significance for chronically disabled individuals with PD. There are not proven treatments for cognitive deficits in this population. The current study will investigate the effectiveness of two different rehabilitation strategies and the potential synergy between them to improve cognitive function and cognitive-related disability in veterans with Parkinson's Disease. The proposed studies could lead to novel clinical interventions for impairment due to cognitive dysfunction in PD.